Plasma von Willebrand factor (vWF) in eleven patients with essential thrombocythemia was studied quantitatively and qualitatively to assess its role in the development of bleeding tendency. Five patients with prolonged bleeding time including three with clinical bleeding tendencies showed decreased ristocetin cofactor (VIIIR:RCo) and factor VIII-related antigen (VIIIR:Ag). On the other hand, six patients without prolongation of bleeding time had normal VIIIR:RCo and VIIIR:Ag. Analysis of vWF multimeric structures by SDSagarose gel electrophoresis revealed lack of the lager multimers in the former group of patients. These abnormalities of plasma vWF were corrected when platelet counts became nearly normal by treatment with busulfan. Infusion of 1-diamino-S-Arginin-Vasopressin improved all the hemostatic abnormalities except for defective platelet aggregation seen in patients with essential thrombocythemia. These results indicate that qualitative and quantitative abnormality of vWF is the main causative factor in development of bleeding tendency in patients with essential thrombocythemia.